A dinuclear copper(II) complex with piperazine bridge ligand as a potential anticancer agent: DFT computation and biological evaluation

• Dinuclear complex [Cu2(bpy)2(im)2(pip)(NO3)2]·2NO3 was synthesized and characterized by elemental analysis and various spectroscopic methods.
• DFT calculations have been performed to obtain optimized structure, harmonic frequencies, IR intensities and energies of frontier molecular orbitals.
• In vitro DNA binding studies were done and revealed strong electrostatic interaction and partial intercalation.
• The complex 1 was assayed for telomerase inhibition using the TRAP-PCR–ELISA assay, SOD activity and anticancer activity.

New dinuclear complex [Cu2(bpy)2(im)2(pip)(NO3)2]·2NO3, 1 was synthesized and characterized by elemental analysis and various spectroscopic methods (IR, 1H and 13C NMR, EPR, UV–Vis, ESI–MS and XRPD). Calculation based on Density functional theory (DFT), have been performed to obtain optimized structure, harmonic frequencies, IR intensities and energies of Frontier molecular orbitals. In vitro DNA binding studies of complex 1 were carried out by employing UV–Vis, fluorescence titrations, isothermal titration calorimetry and circular dichroism that ascertained the strong electrostatic binding interaction of the complex via phosphate backbone of DNA helix as well as partial intercalation. To gain further insight into the molecular recognition toward the target site, interaction studies of complex 1 with 5′-GMP were carried out by UV–Vis titration which revealed higher propensity of 1 towards N7 of guanine base-“5′-GMP”. The DNA cleavage pattern revealed groove binding affinity of the complex 1 towards DNA and suggestive of hydrolytic pathway for the cleavage of pBR322 DNA. The FRET studies at room temperature also confirmed binding of the complex 1 to the CT-DNA. Furthermore, the cytotoxicity of complex 1 was examined on a panel of human tumor cell lines of different histological origins showing significant GI50 values specifically towards MCF7, K562 and A2780 tumor cell lines, Moreover, complex 1 was assayed for telomerase inhibition using the TRAP-PCR–ELISA assay. The results showed complex 1 possessed the most potent telomerase activity (IC50 = 17.1 μM) as well as significant SOD mimics (IC50 ∼ 0.28 μM).

Bimetallic complex 1 was explored as potential cancer chemotherapeutic agents targeting DNA, active site of telomerase and SOD enzyme.Figure optionsDownload as PowerPoint slide